chr16-81096226-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000315467.9(GCSH):​c.53C>A​(p.Ala18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A18V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 8.6e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GCSH
ENST00000315467.9 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.391
Variant links:
Genes affected
GCSH (HGNC:4208): (glycine cleavage system protein H) Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.[provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.095293194).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GCSHNM_004483.5 linkuse as main transcriptc.53C>A p.Ala18Glu missense_variant 1/5 ENST00000315467.9 NP_004474.2
GCSHXM_017023136.3 linkuse as main transcriptc.53C>A p.Ala18Glu missense_variant 1/5 XP_016878625.1
GCSHNR_033249.2 linkuse as main transcriptn.170C>A non_coding_transcript_exon_variant 1/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GCSHENST00000315467.9 linkuse as main transcriptc.53C>A p.Ala18Glu missense_variant 1/51 NM_004483.5 ENSP00000319531 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152032
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
8.60e-7
AC:
1
AN:
1162466
Hom.:
0
Cov.:
27
AF XY:
0.00000178
AC XY:
1
AN XY:
562860
show subpopulations
Gnomad4 AFR exome
AF:
0.0000430
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
152032
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74266
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Benign
0.87
DEOGEN2
Benign
0.12
.;.;.;T;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.43
T;T;T;T;T;T;T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.095
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;.;.;L;.;.;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.2
.;.;.;N;.;.;.
REVEL
Benign
0.045
Sift
Benign
0.25
.;.;.;T;.;.;.
Sift4G
Benign
0.066
.;.;.;T;.;.;.
Polyphen
0.36
.;.;.;B;.;.;.
Vest4
0.14
MutPred
0.28
Gain of solvent accessibility (P = 0.0109);.;Gain of solvent accessibility (P = 0.0109);Gain of solvent accessibility (P = 0.0109);Gain of solvent accessibility (P = 0.0109);Gain of solvent accessibility (P = 0.0109);.;
MVP
0.17
MPC
0.51
ClinPred
0.12
T
GERP RS
-1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.090
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs540997326; hg19: chr16-81129831; API